Thiazole derivatives act on virulence factors of Cryptococcus spp.
Open accessAbstract
Cryptococcosis is an opportunistic or primary fungal infection considered to be the most prevalent fatal fungal disease worldwide. Owing to the limited number of available drugs, it is necessary to search for novel antifungal compounds. In the present work, we assessed the antifungal efficacy of three thiazole derivatives (1, 2, and 3). We conducted in vitro and in vivo assays to investigate their effects on important virulence factors, such as capsule and biofilm formation. In addition, the phagocytosis index of murine macrophages exposed to compounds 1, 2, and 3 and the in vivo efficacy of 1, 2, and 3 in Galleria mellonella infected with Cryptococcus spp. were evaluated. All compounds exhibited antifungal activity against biofilms and demonstrated a reduction in biofilm metabolic activity by 43-50% for C. gattii and 26-42% for C. neoformans. Thiazole compounds promoted significant changes in the capsule thickness of C. gattii compared to that of C. neoformans. Further examination of these compounds suggests that they can improve the phagocytosis process of peritoneal murine macrophages in vitro, causing an increase in the phagocytosis rate. Survival percentage was examined in the invertebrate model Galleria mellonella larvae, and only compound 3 could increase the survival at doses of 5 mg/kg after infection with C. gattii (P = .0001) and C. neoformans (P = .0007), similar to fluconazole at 10 mg/kg. The results demonstrated that thiazole compounds, mainly compound 3, have potential to be used for future studies in the search for new therapeutics for cryptococcosis.
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The macrolides clarithromycin and azithromycin, as well as thiazole derivatives, disrupt the integrity and reduce the thickness of the capsule, resulting in enhanced phagocytosis of Cryptococcus by murine macrophages.
“Finally, the macrolides clarithromycin and azithromycin, as well as thiazole derivatives, disrupt the integrity and reduce the thickness of the capsule, resulting in enhanced phagocytosis of Cryptococcus by murine macrophages59,60”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [60]
Cites
Bacterial biofilms: from the Natural environment to infectious diseases
Hall‐Stoodley, L., Costerton, J. W., & Stoodley, P. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro821 · Cited by 7,133 · see citing works
Perfect, J. R., Dismukes, W. E., Dromer, F., Goldman, D. L., Graybill, J. R., Hamill, R. J., Harrison, T. S., Larsen, R. A., Lortholary, O., Nguyen, M.-H., et al. (2010) · Clinical Infectious Diseases · doi:10.1086/649858 · Cited by 2,660 · see citing works
Park, B. J., Wannemuehler, K. A., Marston, B. J., Govender, N. P., Pappas, P. G., & Chiller, T. M. (2009) · AIDS · doi:10.1097/qad.0b013e328322ffac · Cited by 2,013 · see citing works
Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex
Hagen, F., Khayhan, K., Theelen, B., Kolecka, A., Polacheck, I., Sionov, E., Falk, R., Parnmen, S., Lumbsch, H. T., & Boekhout, T. (2015) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2015.02.009 · Cited by 688 · see citing works
Fungal cell gigantism during mammalian infection
Zaragoza, O., García-Rodas, R., Nosanchuk, J. D., Cuenca-Estrella, M., Rodríguez-Tudela, J. L., & Casadevall, A. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000945 · Cited by 311 · see citing works
Methods for usingGalleria mellonellaas a model host to study fungal pathogenesis
Fuchs, B. B., O’Brien, E., Khoury, J. B. E., & Mylonakis, E. E. (2010) · Virulence · doi:10.4161/viru.1.6.12985 · Cited by 310 · see citing works
Casadevall, A., Cleare, W., Feldmesser, M., Glatman-Freedman, A., Goldman, D. L., Kozel, T. R., Lendvai, N., Mukherjee, J., Pirofski, L.-A., Rivera, J., et al. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.6.1437 · Cited by 298 · see citing works
Musioł, R., Serda, M., Hensel-Bielówka, S., & Polański, J. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710791163966 · Cited by 251 · see citing works
Bergin, D. A., Reeves, E. P., Renwick, J. A. A., Wientjes, F. B., & Kavanagh, K. A. (2005) · Infection and Immunity · doi:10.1128/iai.73.7.4161-4170.2005 · Cited by 250 · see citing works
Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen
Santiago-Tirado, F. H., Onken, M. D., Cooper, J. A., Klein, R. S., & Doering, T. L. (2017) · mBio · doi:10.1128/mbio.02183-16 · Cited by 238 · see citing works
Unusual Features of Pomoviral RNA Movement
Torrance, L., Wright, K. M., Crutzen, F., Cowan, G. H., Lukhovitskaya, N. I., Bragard, C., & Savenkov, E. I. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00259 · Cited by 235 · see citing works
Bicanic, T. A., Wood, R., Meintjes, G., Rebe, K. B., Brouwer, A. E., Loyse, A., Bekker, L., Jaffar, S. S., & Harrison, T. S. (2008) · Clinical Infectious Diseases · doi:10.1086/588792 · Cited by 231 · see citing works
Schmiedel, Y., & Zimmerli, S. (2016) · Swiss Medical Weekly · doi:10.4414/smw.2016.14281 · Cited by 226 · see citing works
Susceptibility of Cryptococcus neoformans Biofilms to Antifungal Agents In Vitro
Martinez, L. R., & Casadevall, A. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.3.1021-1033.2006 · Cited by 200 · see citing works
Meshulam, T., Levitz, S. M., Christin, L., & Diamond, R. D. (1995) · The Journal of Infectious Diseases · doi:10.1093/infdis/172.4.1153 · Cited by 191 · see citing works
Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda
Smith, K. D., Achan, B., Hullsiek, K. H., McDonald, T. R., Okagaki, L. H., Alhadab, A. A., Akampurira, A., Rhein, J., Meya, D. B., Boulware, D. R., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01299-15 · Cited by 191 · see citing works
Induction of Capsule Growth inCryptococcus neoformansby Mammalian Serum and CO2
Zaragoza, Ó., Fries, B. C., & Casadevall, A. (2003) · Infection and Immunity · doi:10.1128/iai.71.11.6155-6164.2003 · Cited by 175 · see citing works
Martinez, L. R., & Casadevall, A. (2005) · Infection and Immunity · doi:10.1128/iai.73.10.6350-6362.2005 · Cited by 166 · see citing works
Consenso em criptococose: 2008
Moretti, M. L., Resende, M. R., Lazéra, M. D. S., Colombo, A. L., & Shikanai‐Yasuda, M. A. (2008) · Revista da Sociedade Brasileira de Medicina Tropical · doi:10.1590/s0037-86822008000500022 · Cited by 138 · see citing works
Biofilm Formation by Cryptococcus neoformans
Martinez, L. R., & Casadevall, A. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mb-0006-2014 · Cited by 119 · see citing works
Zaragoza, Ó., Telzak, A., Bryan, R. A., Dadachova, E., & Casadevall, A. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04928.x · Cited by 87 · see citing works
Negroni, R. (2012) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2012.01.005 · Cited by 86 · see citing works
Fluconazole resistance in cryptococcal disease: emerging or intrinsic?
Cheong, J. W. S., & McCormack, J. (2012) · Medical Mycology · doi:10.3109/13693786.2012.715763 · Cited by 75 · see citing works
Capsule Growth in Cryptococcus neoformans Is Coordinated with Cell Cycle Progression
García‐Rodas, R., Cordero, R. J. B., Trevijano‐Contador, N., Janbon, G., Moyrand, F., Casadevall, A., & Zaragoza, Ó. (2014) · mBio · doi:10.1128/mbio.00945-14 · Cited by 73 · see citing works
Buissa-Filho, R., Puccia, R., Marques, A. F., Pinto, F. A., Muñoz, J. E., Nosanchuk, J. D., Travassos, L. R., & Taborda, C. P. (2008) · Infection and Immunity · doi:10.1128/iai.00349-08 · Cited by 66 · see citing works
Integrated therapy for HIV and cryptococcosis
Srichatrapimuk, S., & D, S. S. M. (2016) · AIDS Research and Therapy · doi:10.1186/s12981-016-0126-7 · Cited by 55 · see citing works
dos Santos, J. R. A., Holanda, R. A., Frasés, S., Bravim, M., Araújo, G. R. D. S., Santos, P. C., da Costa, M. C., Ribeiro, M. J. A., Ferreira, G. F., Baltazar, L. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112669 · Cited by 46 · see citing works
Self-citationThiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro
de Sá, N. P., Lino, C. I., Fonseca, N. C., Borelli, B. M., Ramos, J. P., de Souza-Fagundes, E. M., Rosa, C. A., Santos, D. A., de Oliveira, R. B., & Johann, S. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.07.032 · Cited by 44 · see citing works
Self-citationFungal Polysaccharides: Biological Activity Beyond the Usual Structural Properties
Rodrigues, M. L., Nimrichter, L., Cordero, R. J. B., & Casadevall, A. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00171 · Cited by 43 · see citing works
Revankar, S. G., Fu, J., Rinaldi, M. G., Kelly, S. L., Kelly, D. E., Lamb, D. C., Keller, S. M., & Wickes, B. L. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.112 · Cited by 39 · see citing works
The Pivotal Role of 5-Lipoxygenase-Derived LTB4 in Controlling Pulmonary Paracoccidioidomycosis
Santos, P. C., Santos, D. A., Ribeiro, L. S., et al. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002390 · Cited by 26 · see citing works
Self-citationTratamiento de infecciones fúngicas sistémicas Primera parte: fluconazol, itraconazol y voriconazol
Alberto Fica, C. (2004) · Revista chilena de infectología · doi:10.4067/s0716-10182004000100004 · Cited by 18 · see citing works
Different culture media containing methyldopa for melanin production by Cryptococcus species
Menezes, R. D. P., Penatti, M. P. A., & Pedroso, R. D. S. (2011) · Revista da Sociedade Brasileira de Medicina Tropical · doi:10.1590/s0037-86822011000500012 · Cited by 17 · see citing works
Aimless mutants of Cryptococcus neoformans: Failure to disseminate
Griffiths, E., Kretschmer, M., & Kronstad, J. W. (2012) · Fungal Biology Reviews · doi:10.1016/j.fbr.2012.02.004 · Cited by 15 · see citing works
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Treatment strategies for cryptococcal infection: challenges, advances and future outlook
Iyer, K. R., Revie, N. M., Fu, C., Robbins, N., & Cowen, L. E. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00511-0 · Cited by 363 · see citing works
- Authors
- de Sá, N. P., de Barros, P. P., Junqueira, J. C., Vaz, J. A., de Oliveira, R. B., Rosa, C. A., Santos, D. A., & Johann, S.
- Affiliations
- Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Univ Estadual de São Paulo, São José dos Campos, São Paulo, Brazil
- Universidade Estadual Paulista (Unesp) (BR)
- Universidade Federal de Minas Gerais (BR)
- Department of Pharmaceutical Products, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Corresponding author
- Johann, Susana
- Venue
- Medical Mycology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-19
- Volume
- 57
- Issue
- 1
- Pages
- 84-91
- ISSN
- 0268-1218 (ISSN-L)
- 1369-3786
- 1460-2709
- OpenAlex
- W2792883846
- Cited by
- 13
- References
- 34
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Medical Mycology (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
- Fundação de Amparo Pesquisa Estado de Minas Gerais (FAPEMIG)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
- Pró-Reitoria de Pesquisa da UFMG
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- thiazole derivatives, Cryptococcus gattii, Cryptococcus neoformans, cryptococcosis, antifungal agents, virulence factors, biofilm formation, capsule formation, macrophage phagocytosis, Galleria mellonella model, invertebrate infection model
- MeSH terms
- Animals, Antifungal Agents, Cells, Cultured, Cryptococcosis, Cryptococcus, Disease Models, Animal, Larva, Macrophages, Moths, Phagocytosis, Thiazoles, Molecular Structure, Survival Analysis, Biofilms, Virulence Factors, Mice, Fungal Polysaccharides
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